In the article by Leonardo A. Fernandez et al. entitled Renin-Angiotensin and Development of collateral Circulation After Renal Ischemia, Am.J. Physiol. 243 (Hart, Circ. Physiol. 12) H869-H875, 1982, it is reported that the infusion of angiotensin-II to aortic-ligated left renoprival animals tends to restore blood flow to muscle. From this, the article concludes that after renal ischemia, the renin-angiotensin system, independent of its hypertensive effect, restores blood flow by stimulating the development of collateral circulation.
The resin-angiotensin system is a well-known biochemical pathway in mammals, which is best known for its effect on blood pressure. The renin-angiotensin system also governs the concentration of plasma aldosterone, through which intermediate the potent action of angiotensin II may be effected. However, the exact mechanism of angiotensin II is not known, and the invention of this application is not intended to be limited to any particular theory about mechanisms of operation.
Angiotensin II has been planted into avascular rabbit cornea, and it has been demonstrated that this substance strongly promotes local new blood vessel formation; Fernandez, L. A. et al. Neovascularization Produced by Angiotensin II, J. Lab. Clin. Med. 1985; 105:141-145; Meade Twickler & Fernandez: Neovascularization Produced by Angiotensin II. Fed. Proc. 1982; 41: 12-1230.
It is known that tumors have a capability of inducing the growth of surrounding vascular system to provide the tumor with an adequate supply of blood. In those events where a supporting vascular system does not grow, the size of the tumor is limited by the lack of a supporting blood system.
It has been found that angiotensin II is a very potent angiogenic factor. It can elicit blood vessel growth in the rat cornea when present at extremely low concentrations.